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Aim Although there is much evidence of an antitumor effect of pegylated interferon (IFN)-α-based treatment, limited data is available about that of IFN-β-based treatment. Our goal was to evaluate the impact of IFN-β plus ribavirin (RBV) treatment on the suppression of hepatocellular carcinoma (HCC). Methods This retrospective, multicenter study consisted of 124 chronic hepatitis C patients who were treated with IFN-β plus RBV treatment, including 61 with advanced fibrosis and five with pretreatment HCC. All participants were followed for a median of 2.8 years (range, 2.2–3.2) after the end of their antiviral treatment. The data of 112 patients who finished the treatment were available for analysis. Cox proportional hazard analyses were performed to determine factors significantly associated with HCC development. Cumulative incidence curves for HCC were plotted using the Kaplan–Meier method and differences between groups were assessed using the log–rank test. Results The 2.9% rate of HCC development of patients with sustained virological response (SVR) was significantly lower (P = 0.027) than the 15.9% of non-SVR patients. Interestingly, no significant difference was observed between the rates of HCC development of patients with and without advanced fibrosis (P = 0.733), even though the SVR rate of patients with advanced fibrosis was significantly lower than that of those without advanced fibrosis (P

Background & Aims The effects of pegylated interferon (PegIFN) α and ribavirin (RBV) treatment of chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PegIFNα2b and RBV. Methods This large-scale, prospective, multicenter study consisted of 1013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PegIFNα2b and RBV and the follow-up period started at the end of the antiviral treatment (median observation period of 3.6years). The cumulative incidence rate of HCC was estimated using the Kaplan–Meier method, according to treatment outcome. Results Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than those of the non-virological response (NVR) group (7.6%) ( p =0.003 and p =0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients aged 60years and over, but not for those under 60years of age. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than those of the NVR group (39.4%) ( p =0.03 and p =0.04, respectively). Conclusions SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of HCC development when compared with NVR.

Background and Aims: Pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN α-2b and RBV treatment due to adverse effects in patients with chronic HCV infection. Methods: A total of 2871 Japanese patients who had chronic HCV infection treated with PEG-IFN α-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation. Results: Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms (n = 77, 30.8%), depression-related syndrome (n = 46, 18.4%), hematologic effects (n = 41, 16.4%) and dermatologic effects (n = 27, 10.8%). The rate of discontinuation of treatment for patients aged ≥ 65 years was significantly higher than for patients aged

The aim of this large-scale analysis was to assess the effect of 48-week pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) therapy on virological relapse by patients infected with hepatitis C virus (HCV) genotype 1. The relationship between virological relapse and the dose of PEG-IFNα-2b and RBV was investigated in 619 patients who had once cleared HCV RNA during PEG-IFNα-2b and RBV treatment for 48 weeks. The overall virological relapse rate was 34.1% (211 of 619). The relapse rate was 59.5% (22 of 37) for patients who received

Aim: To investigate the efficacy and safety of a pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). Methods: This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight-based doses of PEG-IFN α-2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target RBV (minimum acceptable dosage). Results: No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (

肝細胞癌に対する経皮的ラジオ波焼灼術（RFA）後に発症した右横隔膜ヘルニアの2症例を経験した．横隔膜の欠損は治療部位に接して生じており，ラジオ波焼灼術による合併症と判断した．RFA治療から発症までの期間は症例1で78週，症例2で112週であった．しかし，横隔膜の断裂は症例1では65週の時点で，症例2では42週の時点でCT上明らかになっていた．横隔膜断裂に加え，肝委縮・腹水貯留・腹圧上昇などにより腸管が横隔膜下腔に入り込むことがヘルニア発症の誘引と考えられた．右葉横隔膜直下の腫瘍に対するラジオ波焼灼術においては，十分量の人工腹水注入や腹腔鏡あるいは開腹下などの横隔膜を損傷しない工夫と治療後の経過観察が重要であると考えられた．

Although there is much evidence of an antitumor effect of pegylated interferon (IFN)-α-based treatment, limited data is available about that of IFN-β-based treatment. Our goal was to evaluate the impact of IFN-β plus ribavirin (RBV) treatment on the suppression of hepatocellular carcinoma (HCC).This retrospective, multicenter study consisted of 124 chronic hepatitis C patients who were treated with IFN-β plus RBV treatment, including 61 with advanced fibrosis and five with pretreatment HCC. All participants were followed for a median of 2.8 years (range, 2.2-3.2) after the end of their antiviral treatment. The data of 112 patients who finished the treatment were available for analysis. Cox proportional hazard analyses were performed to determine factors significantly associated with HCC development. Cumulative incidence curves for HCC were plotted using the Kaplan-Meier method and differences between groups were assessed using the log-rank test.The 2.9% rate of HCC development of patients with sustained virological response (SVR) was significantly lower (P = 0.027) than the 15.9% of non-SVR patients. Interestingly, no significant difference was observed between the rates of HCC development of patients with and without advanced fibrosis (P = 0.733), even though the SVR rate of patients with advanced fibrosis was significantly lower than that of those without advanced fibrosis (P 0.001). Stepwise multivariable Cox analysis extracted that only SVR was significantly associated with HCC development (hazard ratio, 0.20; 95% confidence interval, 0.03-0.84, P = 0.027).SVR was significantly associated with a lower risk of HCC development after IFN-β plus RBV treatment.

Background: It has been suggested that lamivudine therapy may be even more effective if administered at higher doses than is dictated by the current standard regimen. We analyzed the correlation between the effects of lamivudine and body surface area (BSA). Method: We evaluated 134 patients with chronic hepatitis B who had been treated with lamivudine for more than 12 months. The effect of the treatment was evaluated from the levels of serum alanine aminotransferase (ALT) and HBV–DNA. Several variables that could influence the response to treatment, including ALT, albumin, and bilirubin levels, platelet counts, BSA, HBV–DNA, and HBeAg were analyzed. Results: Univariate logistic analysis selected platelet counts, BSA, HBV–DNA and HBeAg in the biological evaluation, and bilirubin, BSA, HBV–DNA and HBeAg in the virological evaluation ( χ 2 > 1.0). Using these factors, multivariate analysis revealed that BSA ( χ 2 = 12.8, p = 0.0004) was the only factor that could contribute significantly to the improvement of ALT levels, and that BSA ( χ 2 = 4.4, p = 0.0354) and HBeAg ( χ 2 = 8.1, p = 0.0044) were independent factors that could influence the suppression of HBV–DNA. Conclusion: We revealed that BSA is a significantly predictor of the effect of lamivudine therapy, suggesting that lamivudine dosage should be based on the individual BSA.

Background and Aim: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. Methods: Eighty-eight patients with chronic hepatitis C who received interferon-α-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of

Interferon monotherapy is considered to have limited effectiveness in patients with HCV of a high viral load. Here, we reported a 21-year old male of chronic hepatitis C with a high viral load of HCV genotype 1b. He received both peg-interferon α-2b plus ribavirin and peg-interferon α-2a plus ribavirin combination therapy. But there were no virological response. Nevertheless, after starting natural interferon α(human lymphoblastoid interferon (HLBI), Sumiferon; Dainippon Sumitomo Pharmaceutical Co., Osaka, Japan), he became HCV-RNA negative at 4 week. The therapy is continued and HCV-RNA negativity is sustained for over 40 weeks. Eradication of HCV might be expected. Natural IFN α contains more than 20 subtypes, and one or more of them may have therapeutic effect against HCV virus of this patient.

A selective and efficient method for disulfide bond formation in peptides utilizing carbon tetrachloride in dichloromethane in the presence of tetrabutylammonium fluoride (TBAF) is described. The reaction proceeded rapidly and no side reaction was observed with nucleophilic amino acids such as Met, His, Tyr or Trp. This method has been applied to three model peptides using solution and on-the-resin disulfide formation.

To shorten the period of interferon (IFN) treatment for chronic hepatitis C, we investigated the clinical efficacy of a regimen using a higher dose and a shorter treatment period. Fifty chronic hepatitis C patients who were hepatitis C virus (HCV)-RNA positive and who were histologically diagnosed as having chronic hepatitis, took part in the study. Virus levels were measured before and 2 weeks after starting the treatment. We administered natural IFNalpha, 10 MU, i.m. daily for 2 consecutive weeks and then three times per week for the subsequent 14 weeks (total dose 560 MU). Patients who were HCV-RNA negative at the completion of the therapy and 6 months later, were evaluated as sustained responders (SR; 32%). Those who were not HCV-RNA negative at the two time points were evaluated as non-responders. Nucleotide and clone differences in the hypervariable region (HVR) and predictive factors for prognosis were also analysed. Low virus level and HCV-RNA genotype 2a/2b were the predictors for good prognosis, whereas the numbers of nucleotide differences and clone differences in HVR were not. Sustained responder patients became HCV-RNA negative 2 weeks after starting the treatment at a significantly higher rate, whereas no non-responder patients were HCV-RNA negative at that time. The SR rate (32%) was equivalent to those reported in previous 24 week treatment studies. This IFN therapy using a higher dose and a shorter period was useful.

The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo, perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 x 10 4 and 5 x 10 4 cells/0.18 mL per cm 2 for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.

We report an autopsy case of hepatocellular carcinoma (HCC) with sarcomatous change arising in the context of primary biliary cirrhosis (PBC) in a 79-year-old man. Primary biliary cirrhosis was diagnosed (stage I according to Scheuer's classification) by findings on blood biochemical analysis, laparoscopy, and liver biopsy at age 69 years. Five years later, (at age 74 years), a mass lesion was detected in the S6 region of the liver by abdominal ultrasonography, and target biopsy revealed well differentiated HCC. Blood biochemistry, ultrasonography, and computed tomography findings showed that the PBC had progressed to stage IV (cirrhotic stage). Percutaneous ethanol injection therapy (PEIT) was administered to the HCC several times over a 5-year period; however, the patient died of liver failure in February, 1994 (at age 79 years). Viral markers for hepatitis B and C were negative during the course, and hepatitis C virus RNA was not detected by polymerase chain reaction. Autopsy findings showed liver cirrhosis and diffuse involvement of spindle-shaped sarcomatoid cells in the liver, particularly in the S6 region, associated with several nodules of trabecular HCC cells. A zone of transition between the sarcomatoid cells and the trabecular hepatocellular carcinoma cells was observed. The sarcomatoid cells were diffusely disseminated in the peritoneal cavity and had metastasized to multiple organs. Immunohistochemically, the cells were positive for fibrinogen, as were the coexisting trabecular hepatocellular carcinoma cells. The HCC had been treated several times with PEIT. Of interest, PEIT may be an important factor in this type of tumor progression.

We examined the protective effects of α-tocopherol against glucose intolerance and mitochondrial damage in rat liver after partial in vivo ischemia and reperfusion, while glucose was intravascularly supplemented. Rats were given α-tocopherol or vehicle for three consecutive days before the experiment. Left and median lobes of the liver received 90-min ischemia and 60-min reperfusion. Besides plasma levels of glucose, insulin, and lipid peroxide, we also measured oxidative phosphorylation, cytochrome c oxidase (CCO) activity, and lipid peroxide levels in mitochondria in both ischemic and non-ischemic lobes of the liver in control and α-tocopherol groups before and at the end of ischemia and after reperfusion. Both plasma glucose and insulin levels after reperfusion were lower in the α-tocopherol-treated group than in the control group. Ischemia markedly suppressed both mitochondrial respiration supported by succinate and CCO activity in the ischemic lobes in both groups. Reperfusion recovered mitochondrial function and CCO activity better in the α-tocopherol-treated group than in the control group, whereas the lipid peroxide levels in both plasma and mitochondria were significantly lower in the α-tocopherol-treated group. In non-ischemic lobes, ischemia-reperfusion slightly accelerated both the oxidative phosphorylation rate (OPR) and CCO activity, whereas lipid peroxide levels were unaffected. The results suggest that glucose intolerance during the early phase of reperfusion was not due to lowered plasma insulin level, but might be related to liver damage, as assessed in terms of mitochondrial functions, in the ischemic lobes. α-Tocopherol could protect against mitochondrial damage and glucose intolerance. Oxidative phosphorylation in non-ischemic lobes likely compensated for the decreased mitochondrial activity in the ischemic lobes during ischemia and reperfusion.

Forty-eight patients with primary biliary cirrhosis (PBC) and 336 healthy individuals were examined for HLA-DR, DQ and DP alleles, by DNA typing based on the polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) method. Frequencies of HLA-DRB1∗1602, DRB1∗0803, DQB1∗0502, DQB1∗0601 and DPB1∗0202 were found to be increased in the patients. These HLA alleles are in linkage disequilibria consisting of DRB1∗1602-DQB1∗0502 and DRB1∗0803-DQB1∗0601-DPB1∗0202 haplotypes. Since the frequencies of DRB1∗1401 and DRB1∗1502, that are in linkage disequilibria with DQB1∗0502 and DQB1∗0601, respectively, were not increased in the patients, the susceptibility to PBC was suggested to be controlled by the HLA-DRB1 locus. In contrast, the frequency of HLA-DQB1∗0302 was decreased in the patients, while the frequency of each DRB1 allele in linkage disequilibria with DQB1∗0302 did not differ significantly between the patient group and control group. This observation suggested that the resistance to PBC may be controlled by the HLA-DQ locus.

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age = 51.7) and 43 patients with HCV-associated HCC (mean age = 62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) (P = 0.001). The relative risk (RR) of association was 12.8 (P = 0.0004) among the males, however, no association was evident among the females, RR = 1.3 (P = 0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.

To investigate the efficacy and safety of a pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight-based doses of PEG-IFN α-2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target RBV (minimum acceptable dosage). No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (65 years old) and total cholesterol (≧220 mg/dL) were significantly independent positive factors associated with an SVR in the NALT group. Twenty-four weeks after treatment, an ALT increase above the normal range was observed for 34.0% (18 of 53) of the non-responsive group of NALT patients. The efficacy and safety of PEG-IFN α-2b plus RBV combination therapy for patients with chronic HCV infection are similar for patients with NALT and those with elevated ALT levels. These results indicate that patients with NALT should be considered for treatment with PEG-IFN α-2b plus RBV.

Pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN α-2b and RBV treatment due to adverse effects in patients with chronic HCV infection.A total of 2871 Japanese patients who had chronic HCV infection treated with PEG-IFN α-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation.Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms (n = 77, 30.8%), depression-related syndrome (n = 46, 18.4%), hematologic effects (n = 41, 16.4%) and dermatologic effects (n = 27, 10.8%). The rate of discontinuation of treatment for patients aged ≥ 65 years was significantly higher than for patients aged65 years, for both men (P0.0001) and women (P = 0.0121). Moreover, the frequency of discontinuation due to neurovegetative symptoms, depression-related syndrome, and hematologic effects for men aged ≥ 65 years was significantly higher than for those aged65 years (P = 0.0001, P = 0.0016, and P = 0.0170, respectively), but not for women.Premature discontinuation due to the adverse effects of PEG-IFN α-2b and RBV treatment by patients with chronic HCV infection is mainly due to neuropsychiatric symptoms and is more common for older than for younger patients.

AIM: To analyze the efficacy and safety of a combination therapy of pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) in older Japanese patients (65 years or older) infected with hepatitis C virus (HCV). METHODS: This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk. RESULTS: At 24 wk after the end of combination therapy, the overall sustained virological response (SVR) for genotypes 1 and 2 were 40.7% and 79.6%, respectively. The SVR rate decreased significantly with age in each genotype, and was markedly reduced in genotype 1 (P < 0.001). Moreover, the SVR was significantly higher in patients with genotype 1 who were less than 65 years (47.3% of 685) than in those 65 years or older (22.9% of 253) (P < 0.001) and was higher in patients with genotype 2 who were less than 65 years (82.9% of 252) than in those 65 years or older (65.6% of 61) (P = 0.004). When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV, the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older (P < 0.001). Adverse effects resulted in treatment discontinuation more often in patients with genotype 1 (14.4%) than in patients with genotype 2 (7.3%), especially by patients 65 years or older (24.1%). CONCLUSION: PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

A 60-year-old woman with hepatic encephalopathy was admitted to our hospital. Ultrasonography, computed tomography and hepatic arteriography revealed diffuse hepatic arteriovenous fistulae (HAVF). Overt portosystemic shunt could not be identified. Right heart catheterization showed increased cardiac output. However the patient had never shown any signs of heart failure. Other than that, marked hepatopetal arterial flow from some branches of the superior mesenteric artery was detected and mesenteric arterial flow remarkably decreased. Extensive HAVF can lead to significant complications, including high output heart failure, pulmonary hypertension, portal hypertension, hepatic encephalopathy, biliary ischemia, cirrhosis, postprandial abdominal pain, and reduced liver function. Embolization or ligation of the hepatic artery provides temporal improvement of clinical symptoms, but long-term results are unsatisfactory because of the development of collateral circulation and the risk of refractory intrahepatic cholangitis, subsequently leading to liver failure. Liver transplantation offers another therapeutic option and can be a successful curative treatment.

Aim: The aim of the present study was to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) and their effectiveness in the treatment of chronic hepatitis C. Methods: Seven hundred and fifteen patients received peg-IFN alpha-2b plus RBV treatment for 48 weeks and 24 weeks for genotypes 1 (n = 586) and 2 (n = 129), respectively. Results: Sustained virological responses (SVR), defined as serum hepatitis C virus (HCV)-RNA undetectable at 24 weeks after the end of treatment, were 42.4% and 74.4% in genotypes 1 and 2, respectively, on an intention-to-treat analysis. SVR significantly increased with treatment length (4.7%, 36.4%, and 51.8% for

Preparation de polystyrenes reticules contenant des groupes chiraux aminoalcool primaires par fixation du groupe chiral lateral sur un polystyrene reactif ou par terpolymerisation d'un monomere chiral avec le styrene et un reticulant. Utilisation comme catalyseurs de l'alkylation enantioselective d'aldehydes par des dialkylzinc. Adaptation de la methode a un systeme de reaction en continu

We reported a case of advanced malignant melanoma with multiple metastases to the liver and the gastrointestinal tract. A 69-year-old man was found to have multiple liver tumors and was referred to our hospital. He had a history of chronic hepatitis C, but HCV-RNA was negative and AFP and PIVKA-II were not elevated. Metastatic liver tumors were suggested by abdominal dynamic CT and ultrasonography. Multiple small blackish spots were detected in the gastrointestinal tract. Malignant melanoma was diagnosed by biopsy from the liver tumor and the gastrointestinal tract and remarkable elevation of 5-S-CD 436.4 nmol/l. A blackish, slightly elevated lesion was detected in the oral cavity and was thought to be primary site. The patient chose palliative therapy and died 69 days after his first visit to his local doctor.

Recently electrocardiogram measurement with electrostatic capacity type electrode has been researched. Electrocardiogram can be measured by bringing the metal plate close from the outside of the body to the vicinity of the heart and amplifying the voltage. Metal plate is not necessary to be attached to the skin, and this measurement is a complete no contact measurement of an electrical signal in vivo.

We have studied the capacitive coupling ECG measurement as a new emotional communication between man and machine. In this capacitive coupling measurement a metal plate is placed outside the body and this plate and the electric signal source inside body forms a condenser and the electric biosignal can be derived through this condenser. In this paper, we studied ECG measurement using two or only one capacitive coupling electrodes without any ground electrode for more convenient ECG monitoring. Three ECG measurement methods different in the setting of capacitive coupling electrodes and ground electrode were tested as follows; two isolated signal electrodes with an isolated ground electrode, two isolated signal electrodes without any ground electrode and one isolated signal electrode without any ground electrode. As a result, two isolated electrodes are enough to measure ECG whether with a ground electrode or not. Moreover ECG can be measured with only one signal electrode. Of course ECG waveform was noisy but "R" peak of ECG could be detected. Same tendencies were confirmed in all five subjects participated in experiments.

The aim of the present study was to assess the efficacy of the prolonged interferon monotherapy following combination treatment. Seventy-six patients were enrolled. Of these, 7 were withdrawn while undergoing treatment with interferon combined with ribavirin, and 12 remained positive for HCV-RNA at the completion of the combination treatment. We studied 57 Japanese patients with chronic hepatitis C due to genotype 1b HCV of a high viral load. These patients tested negative for HCV-RNA at the completion of the combination treatment for 24 weeks. After the combination treatment, 29 patients of the prolonged treatment group successively received interferon-alpha monotherapy for 24 weeks, while 28 patients in the combination treatment alone group received no medication. The rate of a sustained virologic response (SVR) was higher in the prolonged treatment group (41%, 12/29) than in the combination treatment alone group (25%, 7/28), but not significantly. Patients who became HCV-RNA negative by 4 weeks after the start of the combination treatment showed an SVR rate of 86%. The prolonged treatment resulted in SVR in all five patients who newly became HCV-RNA negative at 12 weeks. In conclusion, the prolonged treatment was effective for patients who newly became HCV-RNA negative at 12 weeks.

A 21-year-old man was referred to our hospital because of a liver mass lesion detected by abdominal ultrasonography. He had received no hormonal treatment. Physical examinations revealed no abnormalities, and laboratory data, including hepatic function test results, were within normal ranges, with the exception of elevated levels of serum protein induced by vitamin K absence or antagonist (PIVKA)-II (2.2 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass lesion measuring 10 x 10 cm, with hypoechoic areas located in the right posterior segment of the liver. A low-density area and a hypervascular area were detected in the right posterior segment of the liver by computed tomography and celiac angiography, respectively. As hepatocellular carcinoma could not be completely excluded, the tumor was resected. The tissue consisted of sheets of tumor cells with eosinophilic cytoplasm and round nuclei showing a thin trabecular pattern, and these histological findings indicated liver cell adenoma. After resection of the tumor, serum PIVKA-II returned to the normal level.

Preparation de polystyrenes reticules contenant des groupes chiraux aminoalcool primaires par fixation du groupe chiral lateral sur un polystyrene reactif ou par terpolymerisation d'un monomere chiral avec le styrene et un reticulant. Utilisation comme catalyseurs de l'alkylation enantioselective d'aldehydes par des dialkylzinc. Adaptation de la methode a un systeme de reaction en continu

AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P

To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation.We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249), two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA, as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed.For 1-year treatment, multivariate analysis revealed that BSA (P = 0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA (P = 0.0147) was the only factor for the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels.BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

症例は53歳,男性.全身倦怠感と露出部の皮膚症状を主訴として来院した.検査所見では軽度の肝機能障害ならびに尿中ポルフィリン体の排泄増加がみられた.腹腔鏡検査では肝表面に灰青色斑がみられ,生検肝は紫外線の照射によって赤色蛍光を発した.肝組織像では軽度のリンパ球浸潤,ヘモジデリンの沈着および多数の細胞質内針状結晶を認めた.症候性晩発性皮膚ポルフィリン症と診断し,昭和56年12月より4～8週おきに1回250～300ml,総量3,000mlの瀉血療法を行った.治療にほぼ平行して自覚症状の軽減,尿中ポルフィリン体排泄量の正常化がみられたが,肝機能検査成績はほとんど不変であった.治療終了6カ月後に行われた腹腔鏡検査では,肝の灰青色斑は消失し,生検肝の赤色蛍光もみられなくなったが,肝組織の炎症像および針状結晶については不変であった.本例において瀉血療法は体内の過剰な蓄積ポルフィリン体の減少と,皮膚所見および自覚症状の軽減という点では著効を示したといえよう.

The surface changes of acute centrolobular and perilobular necrosis were studied in rat liver using peritoneoscopy. Centrolobular necrosis was induced by carbon tetrachloride and perilobular necrosis by allyl formate. Vessels observed on the control rat liver surface were identified as terminal hepatic veins by irrigation of the hepatic vein with a barium solution. Polygonal whitish markings were observed on the liver surface 48 hours after carbon tetrachloride administration. Terminal hepatic veins were regularly distributed throughout the central portions of the whitish areas. Reddish spots about 0.1 mm in diameter were scattered about the terminal hepatic veins. The reddish spots and whitish areas corresponded to the histological findings of central liver cell necrosis and infiltration by Kupffer and white blood cells. Six hours after allyl formate administration, round reddish spots about 0.3 mm in diameter were regularly distributed on the liver surface among the terminal hepatic veins. These spots corresponded to the histological findings of liver cell necrosis around the portal area. In summary, acute centrolobular and perilobular liver cell necrosis were newly observed as reddish spots by peritoneoscopy.

Summary Three monoclonal antibodies against human interleukin-6 were established and characterized. One antibody was shown to strongly neutralize both the Ig-inducing and hybridoma/plasmacytoma growth activity of interleukin-6. The results of its epitope analysis using protease treated interleukin-6 and immobilized antibody indicated that this neutralizing antibody binds to a peptide corresponding to Leu151-Lyauthor71 of interleukin-6 molecule. Further analysis using synthetic peptides showed that a shorter peptide corresponding to Ala153-Thr162 can also inhibit the binding of the antibody to interleukin-6. These results suggest that this carboxyl-terminal region plays a crucial role in interleukin-6 functions.

生前異所性ACTH, β-MSH産生悪性胸腺腫と診断し,試験切除による一部腫瘍切片の光顕および電顕的検索から悪性胸腺carcinoidと診断された興味ある症例を経験したので,剖検所見と共に症例の概要を紹介し,文献的考察を加えた.症例は68才,男子で胸部X線異常陰影の精査と下腿浮腫を訴え入院.典型的Gushing症候群やcarcinoid症候群を示唆する所見はない.胸部X線縁で左側上前縦隔に直1Ocmの巨大な腫瘤陰影を認め,選択的胸腺静脈撮影により悪性胸腺腫が示唆された.尿中17-OHCS, 17-KS共に著増し,血中cortisol, ACTH, β-MSH (9am)も共に高値で日内変動を認めず, dexamethasone lmg, 4mg法の抑制試験は共に陽性, rapid ACTH試験で過大反応を示す.入院40日後突然,低K血性アルカローシス,尿糖,高血糖,高血圧などが出現し,異所性ACTH, β-MSH産生悪性胸腺腫の診断のもとに開胸手術を行なうも高度の癒着のため試験切除の施行にとどめた.術後9日目に肺水腫を来たし死亡した.病理組織学的に原発腫瘍は神経細胞由来の腫瘍に酷似し,索状配列,中心壊死,石灰沈着,ロゼット形成を示し, argyrophil顆粒陽性,電顕的にも豊富な分泌穎粒が確認され,胸腺carcinoidと診断された.また本腫瘍中よりACTH, β-MSHおよびserotoninが証明され,剖検で副腎の結節性過形成および下垂体β細胞のCrooke変性とACTH含量の著減が証明された.異所性ACTH産生腫瘍とPearseのAPUD系細胞由来carcinoidとの関連,および異所性ACTH産生胸腺腫瘍の本邦報告例をまとめ考察を加えた.

When THF–borane (1/1) and aromatic ketone were supplied continuously to the column containing polymer-supported (S)-(−)-2-amino-3-(p-hydroxyphenyl)-1,1-diphenyl-1-propanol, the chiral product, secondary benzylic alcohol, could be obtained successfully (>90% ee). Large quantities of highly optically pure alcohol could be produced by the continuous flow system by the use of only a small amount of polymeric auxiliary.

脳腫瘍,脳炎,外傷などで視床下部性の多食症が生じることが報告されているが,脳への腫傷塞栓後に起こった報告はない.症例は55才,男性.原発性肝細胞癌の診断で入院治療中,左不全片麻痺,右動眼神経麻痺,左小脳失調が出現し,翌日より多食となり, 4日間で体重が3kg増加した.性欲亢進,情動変化, oral tendencyはなく,肝不全で死亡.剖検では肝細胞癌を伴う甲型肝硬変で,門脈,肝静脈は腫瘍により閉塞されていた.右中脳上丘レベルで動眼神経核,赤核に腫瘍梗塞を認め,右視床下部腹内側核の神経細胞変性とグリオーシスがみられた.多食の起こり方から,その原因を梗塞部に軸索を出している腹内側核細胞の逆行性変性によるものと考えた.

Background Lamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Δ-albumin) and various pretreatment variables. We also analyzed the correlation between Δ-albumin and the reduction in serum levels of HBV-DNA (Δ-HBV-DNA) or alanine aminotransferase (Δ-ALT) at month 12. Results The average Δ-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Δ-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Δ-albumin and either pretreatment alanine aminotransferase levels or Δ-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Δ-albumin and both pretreatment serum HBV-DNA levels and Δ-HBV-DNA. Conclusion Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.